5-amino-N-tert-butyl-2-(methylthio)-4-(3-(2-oxo-2-(prop-2-ynylamino)ethylamino)phenyl)thieno[2,3-d]pyrimidine-6-carboxamide | 1186404-09-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-amino-N-tert-butyl-2-(methylthio)-4-(3-(2-oxo-2-(prop-2-ynylamino)ethylamino)phenyl)thieno[2,3-d]pyrimidine-6-carboxamide
• 英文别名: 5-amino-N-tert-butyl-2-methylsulfanyl-4-[3-[[2-oxo-2-(prop-2-ynylamino)ethyl]amino]phenyl]thieno[2,3-d]pyrimidine-6-carboxamide
• CAS: 1186404-09-0
• 化学式: C₂₃H₂₆N₆O₂S₂
• 分子量: 482.63
• InChiKey: OBTDWDIYUNCNGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  176
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-amino-N-tert-butyl-2-(methylthio)-4-(3-(2-oxo-2-(prop-2-ynylamino)ethylamino)phenyl)thieno[2,3-d]pyrimidine-6-carboxamide 、 (S)-N-(1-acetyl-4-(4-((1-(2-(2-(2-azidoethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2,2,4-trimethyl-1,2,3,4-tetrahydroquinolin-6-yl)-[1,1'-biphenyl]-4-carboxamide 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Development of Selective LH Receptor Agonists by Heterodimerization with a FSH Receptor Antagonist

  摘要：

  The structural resemblance of the luteinizing hormone receptor (LHR) and follicle stimulating hormone receptor (FSHR) impedes selective agonistic targeting of one of those by low molecular weight (LMW) ligands. In the present study we describe a series of dimeric ligands consisting of a LMW agonist with dual activity on the FSHR and the LHR linked to a selective FSHR antagonist. Biological evaluation shows these compounds to be potent and selective LHR agonists since no agonistic activity on the FSHR was observed. Equimolar mixing of the monomeric counterparts did not yield the pharmacological profile observed for the heterodimeric ligands, and FSHR agonism of the monomeric LHR agonist was still observed. The here-described results show that ligands with unique pharmacological profiles can be obtained by dimerizing monomeric molecules with distinct opposite properties.

  DOI：

  10.1021/ml100229v

文献信息

• Oligoproline helices as structurally defined scaffolds for oligomeric G protein-coupled receptor ligands
  作者：Kimberly M. Bonger、Varsha V. Kapoerchan、Gijsbert M. Grotenbreg、Chris J. van Koppen、C. Marco Timmers、Gijsbert A. van der Marel、Herman S. Overkleeft

  DOI：10.1039/b923556f

  日期：——

  Oligoprolines (OPs) are used as rigid backbone scaffolds for the design of oligomeric ligands that target specific G protein-coupled receptors. The OPs were designed to vary in length, the position and number of the ligand-functionalized residues incorporated. For all synthesized compounds a typical PP type II helix was evidenced by circular dichroism indicating that decoration of the helix with large ligands did not affect the helical conformation. Pharmacological evaluation revealed that oligomerization of an agonist with the use of an oligoproline scaffold showed an increase in potency when compared to the monomeric counterparts.

  寡脯氨酸（OP）被用作刚性骨架支架，用于设计针对特定G蛋白偶联受体的寡聚配体。OP的设计在长度、位置和结合的配体官能团残基数量方面各不相同。对于所有合成的化合物，典型的PP II型螺旋通过圆二色性得到证实，表明用大配体修饰螺旋不会影响螺旋构象。药理学评估显示，与单体配体相比，使用寡脯氨酸支架的激动剂寡聚化显示出更强的效力。
• Development of Selective LH Receptor Agonists by Heterodimerization with a FSH Receptor Antagonist
  作者：Kimberly M. Bonger、Sascha Hoogendoorn、Chris J. van Koppen、C. Marco Timmers、Gijsbert A. van der Marel、Herman S. Overkleeft

  DOI：10.1021/ml100229v

  日期：2011.1.13

  The structural resemblance of the luteinizing hormone receptor (LHR) and follicle stimulating hormone receptor (FSHR) impedes selective agonistic targeting of one of those by low molecular weight (LMW) ligands. In the present study we describe a series of dimeric ligands consisting of a LMW agonist with dual activity on the FSHR and the LHR linked to a selective FSHR antagonist. Biological evaluation shows these compounds to be potent and selective LHR agonists since no agonistic activity on the FSHR was observed. Equimolar mixing of the monomeric counterparts did not yield the pharmacological profile observed for the heterodimeric ligands, and FSHR agonism of the monomeric LHR agonist was still observed. The here-described results show that ligands with unique pharmacological profiles can be obtained by dimerizing monomeric molecules with distinct opposite properties.